(a) Field of the Invention
This invention relates to [5(or 4)-(pyridinyl)-2-pyrimidinyl]ureas and their cardiotonic use.
(b) Information Disclosure Statement
N-[4-(4-pyridinyl)-2-pyrimidinyl]urea (no. 4k) was reported by Bennett et al. [J. Med. Chem. 21(7), 623-8 (1978)] as producing a reduction in paw volume of 12% at 100 mg/kg in the carrageenan foot edema test in the rat. Compound no. 4k was prepared by hydrolysis of the corresponding N-cyano-4-(4-pyridinyl)-2-pyrimidinamine (4f). Other compounds disclosed include, inter alia, 4-(4-pyridinyl)-2-pyrimidinamine (4a), 4-(3-pyridinyl)-2-pyrimidinamine (4e) and N-methyl-4-(4-pyridinyl)-2-pyrimidinamine (4g), Discussion in the Bennett et al reference regarding the antiinflammatory activity of the compounds disclosed therein concluded as follows:
"None of the compounds tested against adjuvant-induced edema in the rat displayed a level of activity sufficient to warrant further investigation. Based on additional testing it would appear that these compounds represent a series of false positives in the carrageenan-induced edema model."
Isomeric N--R--N'--[2-(4-,3- or 2-pyridinyl)-4-pyrimidinyl]ureas, useful as allergy inhibitors, are disclosed and claimed in Lesher and Singh U.S. Pat. No. 4,008,235, issued Feb. 15, 1977, and in a Lesher, Singh and Mielens publication [J. Med. Chem. 25(7), 837-842 (1982)].